Background/Objectives: Hyperfunctioning thyroid nodules are generally considered to have a low malignancy risk, but data on genuine hyperfunctioning thyroid neoplasms remain limited. This study aimed to characterize the clinicopathologic features and diagnostic implications of true hyperfunctioning thyroid neoplasms through lesion-level imaging-pathologic correlation and to estimate their observed frequency within a surgically treated cohort. Methods: We retrospectively reviewed 82 hyperthyroid patients at our institution with thyroid scintigraphy suggestive of solitary or multiple toxic nodules between 2014 and 2024; 25 underwent thyroidectomy. True hyperfunctioning thyroid neoplasms were defined by lesion-level imaging-pathologic correlation. Results: Among the 25 surgically treated patients, seven had confirmed hyperfunctioning carcinoma or tumors of uncertain malignant potential (UMP) (28.0%; 95% CI, 14.1–47.8%). When referenced against the full scintigraphic cohort of 82 patients, of whom only 30.5% underwent surgery, the observed rate was 8.5% (95% CI, 4.2–16.6%); however, this figure should be interpreted with caution given the inherent surgical selection bias. Four patients had overt carcinomas. The remaining three patients had UMPs. In nodule-based analysis, hyperfunctioning neoplasms were significantly larger than coexisting tumors (5.0 ± 2.8 vs. 0.8 ± 0.7 cm, p = 0.007) and more often follicular-patterned (85.7% vs. 27.3%; RR, 3.14; 95% CI, 1.14 to 8.64; p = 0.0498). Conclusions: These findings indicate that hyperfunctioning status does not definitively exclude malignancy, while also emphasizing that the absolute malignancy frequency in unselected hyperthyroid populations remains uncertain.
Huang et al. (Sat,) studied this question.